Atorvastatin and sildenafil improves hypertension in rats exposed for seven days to low lead levels

Atorvastatin and sildenafil improves hypertension in rats exposed for seven days to low lead levels

• Autor
• Ediléia de Souza Paula
• Co-autores
• Gabriela Palma Zochio , Carlos Alan Candido Dias Junior
• Resumo

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  Introduction: Exposure to low lead (Pb) levels has been associated with cardiovascular disorders, including hypertension. In search of pharmacological agents to attenuate Pb-induced hypertension, drugs that activate NO pathway may have this therapeutic potential, for example: atorvastatin and sildenafil. Atorvastatin upregulates NO synthesis and sildenafil inhibits cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5 (PDE5). Methods: Male Wistar rats (250-400g) were distributed into four groups: Pb+atorvastatin (Pb+Atorva), Pb+sildenafil (Pb+Sild), Pb+saline (Pb) and saline+sodium acetate (Sham). Pb+Atorva, Pb+Sild and Pb rats received Pb acetate (8µ?/100g of body weight) on the first day of the protocol. Pb levels were maintained with Pb acetate (0.1µ?/100g/day) for consecutive seven days. Pb (or sodium) acetate was intraperitoneally (i.p) administrated. Atorvastatin (20mg/kg/day) and sildenafil (15mg/kg/day) or saline (0.5 mL/Kg/day) were administrated by gavage once daily. Systolic blood pressure (SBP) was measured by tail cuff plethysmography every day until the eighth day, when the animals were killed. Vascular reactivity experiments were performed in thoracic aorta rings with intact and mechanically removed endothelium. Aorta rings were submitted to cumulative concentration-response curves to potassium chloride (KCl, 10-120 mM) and phenylephrine (Phe, 10^-10-10^-4 M). To examine endothelial function, aorta rings were pre-contracted with Phe (10^-6 M) followed by cumulative concentration-response curves to acetylcholine (ACh, 10^-9-10^-5 M) in absence (or presence) of N(G)- Nitro-L-arginine methyl ester (L-NAME, 10^-4 M). Results: Atorvastatin and sildenafil prevented increases in SBP on day 6 and 7 compared to Pb group. Sham group showed no change in SBP throughout the experimental period. Moreover, no significant differences were found in KCl and Phe-induced contractions from all groups. However, impaired relaxation induced by ACh was found in aorta rings from Pb and Pb+Atorva groups, while sildenafil prevented this effect. Conclusion: Atorvastatin and sildenafil treatments protect against Pb-induced hypertension, while sildenafil but not atorvastatin prevents endothelial dysfunction caused by Pb.

   

• Palavras-chave
• Lead, Hypertension, Vascular Reactivity
• Modalidade
• Vídeos
• Área Temática
• Estresse oxidativo